Method for neuromodulation treatment of neurodegenerative disease

ABSTRACT

The present disclosure provides a neuromodulation method for treating neurodegenerative disease. The neuromodulation method comprises attaching a first active electrode to a patient&#39;s leg in the back of the knee area in an expected location of a peroneal nerve of the first leg and attaching a grounding electrode to the patient&#39;s body. Generating electrical pulses by a pulse generator connected to the first active electrode and the grounding electrode. Stimulating by the first active electrodes the peroneal nerve of the first leg and controlling via a control unit a flow of the generated pulses to the first electrode.

CROSS-REFERENCE TO RELATED APPLICATION

This Application is a continuation-in-part patent application under 35USC § 121 claiming priority to U.S. non-provisional patent applicationSer. No. 16/339,790 filed on Apr. 5, 2019 which was a U.S. nationalphase filing under 35 USC § 371 of International Patent Application No.PCT/CZ2016/000113 filed on Oct. 5, 2016.

FIELD OF THE TECHNICAL DISCLOSURE Technical Field

The present disclosure relates to a medical method for a neuromodulationtreatment of a patient.

Background of the Disclosure

Use of an electrical stimulation of neurons for the benefit of a humansubject is described to treat incontinence, to stimulate muscles for thepurpose of simulating exercise and subsequent increase of heart rate, toimprove lymphatic drainage of the lower limbs, to stimulate neurons, andfor other related applications associated with the positive effects ofapplied electric current to human body.

For instance, a percutaneous tibial nerve stimulation (PTNS) method fortreating incontinence uses a needle introduced in close proximity of thenerve in the ankle region, and by means of an electric current connectedthereto, it stimulates the nerve as well as the adjacent nerves in thepelvic area. Such repeated stimulation of the pelvic region can have asignificantly positive effect on both the functioning of muscles and thecommunication between the patient's body and nervous system. Improvementof a bladder function by a nerve stimulation using an electrical currentdelivered to the proximity of the nerve via a body invasive needle maybe achieved by repeated sessions each lasting several minutes. Thehistoric disadvantages of inserting needles into the patient's bodyinclude mainly pain, the risk of infection and nerve damage, and also arequirement of a medical professional to carry out the treatment.Additionally, for a successful treatment, it is important to ensure anaccurate targeting of the nerve to be stimulated. In practice, thesubjective feeling of the patient is used. However, this is not alwaysaccurate, and it has proven to be the biggest obstacle in impactingsuccess rates of the treatment.

Whilst the use of a neuromodulation technology is known for anincontinence treatment an effective neuromodulation method and a devicefor a treatment of variety of neurodegenerative diseases is still leftto be invented.

SUMMARY OF THE DISCLOSURE

One objective of the present disclosure is to remedy the drawback andprovide an effective neuromodulation method and a device for a treatmentof variety of neurodegenerative diseases.

An aspect of the present disclosure provides a device for stimulatingthe peripheral nerves, comprising a memory unit, at least one electrodeattached to the patient's body for generating pulses, a control unitconnected to the electrode for setting at least one electrode pulseparameter, and further connected to at least one response detector toneuromodulation. The response detector to neuromodulation is connectedto a control unit for transmitting information on the frequency ofmovement of at least a part of the patient's body. The control unit ofthe device further sets the flow of current of electrode pulsesautomatically, depending on information about the frequency value ofmovement of at least a part of the patient's body.

The control unit receives information on the frequency value from theresponse detector to neuromodulation, or from memory. The detector ofthe device can be an optical sensor, an infrared sensor, anaccelerometer, or a capacitive, inductive, thermal, flow, ultrasound, ormagnetic sensor. In an alternative embodiment of the present disclosure,an electromyograph can also be used as a detector. In a preferredconfiguration, the detector can make use of more than one sensor.

The memory device can be at least one of the following: an HDD disk, SSDdisc, flash memory, memory card, RAM, CD, DVD, or Blu-ray. Inalternative configurations, the memory can be a remote storage deviceaccessible through a network service.

Alternatively, the remote memory storage unit can be accessible throughanother neuromodulation device connected to the network service.

The control unit may change the frequency of the electrode pulses untilit substantially equals the frequency of the recorded movements. Thecontrol unit may also change the flow of the current of pulses until theoptimum frequency of recorded movement is reached.

The device can include one or more control units, which are separated.The control unit can be a part of the controller, which may furthercomprise a display device and user input for the operator. The controlunit, according to the present disclosure, sets the frequency of thepulses in a range between 0.1 and 100 Hz and sets the length of thepulses in a range between 0.1 and 10 ms. The control unit, as per thepresent disclosure, may further set the shape of the pulse. The controlunit of the present device may further set the polarity of the voltageranging from positive to negative.

The control unit may communicate with a database stored in the memory,which is the internal memory of the control unit, or in a remote storageunit, available via network services. Here it may store the informationon recommended parameters of the flow of the current of pulses. Thedatabase may further include the patient's personal data, such as butnot limited to: information on the patient's age, sex, information onidentity and personal data of the patient, for example identificationnumber, number of the insurance, address, social security number, creditcard number and so on. As per the present disclosure, the control unitmay send the information from the database to the remote storage. As perthe present disclosure, the detector and the controller may be parts ofa single construction. In one aspect, the controller and at least one ofthe electrodes may be parts of a single unit. Such single unit can be adevice electrically and mechanically connected. In some aspects, asingle unit may be also integrated in a single construction.

A further aspect of the present disclosure provides a method for aneuromodulation treatment of a low urinary tract dysfunction that mayinclude treatment of symptoms of an overactive bladder and/or fecalincontinence in humans. The inventors surprisingly found the abovedefined method may be also applicable for a neuromodulation treatment ofthe neurodegenerative diseases such as Parkinson's, Alzheimer's andpotentially also Huntington's disease, Amyotrophic lateral sclerosis(ALS), Motor neuron disease and other neurodegenerative diseases.

Particularly, the method involves a control unit and a one activeelectrode or at least two active electrodes capable of generatingelectrical pulses. The at least two active electrodes are attached tothe patient's body, so that a first active electrode of the at least twoactive electrodes is attached to either of the patient's legs and asecond active electrode of the at to least two active electrodes is alsoattached to either of the patient's legs. The first active electrode ofthe at least two active electrodes may be attached to a first patient'sleg in the back of the knee area in an expected location of a peronealnerve of the first leg. The second active electrode of the at least twoactive electrodes may be attached to a second patient's leg in the backof the knee area in an expected location of a peroneal nerve of thesecond leg.

Alternatively, the first active electrode may be attached to the firstleg of the patient and the second active electrode is also attached tothe same leg. The first active electrode may be attached to the back ofeither knee and the second active electrode is attached to the back ofthe other knee.

After the active electrodes are attached, the first electrical pulses inthe first active electrode may be delivered to the patient's body, andat the same time or subsequently, other electrical pulses in the secondactive electrode may be delivered to the patient's body. In thefollowing step, the flow of the pulse current may be set. The preferredmethod further involves a step of synchronizing the timing of eachpulse.

In one aspect the active electrodes are attached in the proximity ofbranches of a peripheral nerve.

The active electrodes may be attached to the patient so that the firstactive electrode may be attached to the first branch of the sciaticnerve and another, second, active electrode may be attached to anotherbranch of the sciatic nerve. Preferably, one of the following nerves isstimulated: the lumbosacral plexus, sciatic nerve, common peronealnerve, tibial nerve, pudendal nerve, superior gluteal nerve, inferiorgluteal nerve, posterior cutaneous femoral nerve, obturator internusnerve, piriformis, quadratus femoris nerve, plantar nerve, coccygealnerve. In preferred embodiment, pudendal nerve or tibial nerve or commonperoneal.

In one aspect, the first active electrode may be attached to one leg ofthe patient and the second active electrode may be attached to the otherleg of the patient. In another aspect of to the present method, thefirst active electrode may be attached to the first leg of the patientand the second active electrode is also attached to the same leg of thepatient.

The active electrodes are, according to the present disclosure,transcutaneous, percutaneous or electrodes for long term implantation.In one aspect of the present method, the first active electrode may beattached to the back of either knee and the second active electrode maybe attached to the back of the other knee. Synchronization of theelectrical pulses delivered to patient via the first and the secondactive electrodes may be achieved by timing the pulses to beginning ofeach pulse. The timing of pulses may be synchronized per the time ofdelivery of the pulse from the first active electrode and the time ofdelivery of the pulse from the other active electrode into the targetarea. The target area may be a sacral plexus or a sciatic nerve. Themethod, further involves placing a grounding electrode onto thepatient's body, most advantageously on the patient's suprapubic,hypogastric or sacral area.

The electrical pulses may have, a frequency between 0.1 Hz and 100 Hz, apulse width between 0.1 ms and 5 ms, a current between 0 mA and 250 mAand a voltage between 0 V and 90 V. The frequency of the electricalpulses may be set between 2.5 Hz and 60 Hz and the pulse width ofelectrical pulses may be between 0.1 ms and 2.5 ms. Each of the activemay have an active surface greater than 0.3100 square inch (2 cm²), theelectrical pulses may have have a current between 15 mA and 250 mA.Alternatively, each of the active electrodes may have an active surfacebetween 0.0775 square inch (0.5 cm²) and 0.3100 square inch (2 cm²), theelectrical pulses may have a current between 0 mA and 15 mA.Alternatively, each of the active electrodes may have an active surfaceless than 0.0775 square inch (0.5 cm²), the electrical pulses may have acurrent between 0 mA and 5 mA.

The electrical pulses may have substantially a rectangular orright-triangular shape and are monophasic or biphasic. The time of thepulses may be determined by an algorithm stored in the control unit'smemory.

The method may further include the following steps for a precisepositioning of the first and second active electrode. After attachmentof any of the active electrodes, the electric pulses are generated, andthen reflex movements of at least one part of the patient's body may bemonitored. The sufficiency of the reflex movements of the monitored partof patient's body may be determined. If the reflex movements of themonitored part of the patient's body are insufficient, the activeelectrode is repositioned. The steps may be repeated until the reflexmovements of at least one part of the patient's body are sufficient andthus the optimal location is found for the active electrode. The methodmay further include collecting information about the use of theneuromodulation medical device as described above, other similarneuromodulation devices or other medical devices. The method mayinvolves collecting information from the control unit. The informationmay be sent from the control unit to a memory. The information may bestored in a database. The information may be retrieved from saiddatabase. The medical device as describe above may be a therapeuticmedical device, a surgical medical device or a diagnostic medicaldevice. The control unit can communicate with the memory using any ofthe following means: GSM, Bluetooth, radio frequency, infraredcommunication, LAN, USB or a wireless internet connection. The methodmay further involve assigning an identification number to a patient,medical device or the information. The method may further involve stepsof storing the information in the memory of the device and connectingthe medical device to another medical device. The information mayconcern an undergone treatment and involve at least information on thepulse current flow, current intensity, the frequency of pulses. Themethod may further involve evaluating the information stored in thedatabase and may use said information for invoicing. The method mayfurther involve using the information stored in the database and sendthe information to the patient's physician and/or to the patient'selectronic medical chart. The method may further involve using theinformation stored in the database to automatically alter the parametersof the treatment or use of the device.

BRIEF DESCRIPTION OF THE DRAWINGS

Other features and advantages of the invention appear from the followingdetailed to description of some of its embodiments, given by way ofnon-limiting example, and with reference to the accompanying drawings,in which:

FIG. 1 shows a side view of the first embodiment of the electrode.

FIG. 2 shows a bottom view of the first embodiment of the electrode.

FIG. 3 shows a magnetic field emitted by the first embodiment of theelectrode.

FIG. 4 shows a side of an alternative embodiment of the electrode.

FIG. 5 shows whole device as per the present disclosure.

FIG. 6 shows an assembly of the optical sensor in the detector.

FIG. 7 shows an assembly of the ultrasonic sensor in the detector.

FIG. 8 depicts an exemplary statistically adjusted functional magneticresonance images (fMRIs) performed on subjects without the actualneuromodulation.

FIG. 9 depicts an exemplary statistically adjusted results of fMRIsperformed on subjects during the neuromodulation.

FIG. 10 depicts an exemplary statistically adjusted results of fMRIsfocused on detailed analysis of basal ganglia during theneuromodulation.

DETAILED DESCRIPTION OF THE DISCLOSURE

The foregoing summary, as well as the following detailed description ofcertain examples will be better understood when read in conjunction withthe appended drawings. As used herein, an element or step recited in thesingular and proceeded with the word “a” or “an” should be understood asnot excluding plural of the elements or steps, unless such exclusion isexplicitly stated. Further, references to “one embodiment” are notintended to be interpreted as excluding the existence of additionalembodiments that also incorporate the recited features. Moreover, unlessexplicitly stated to the contrary, embodiments “comprising” or “having”an element or a plurality of elements having a particular property mayinclude additional elements not having that property.

In the figures, the same references denote identical or similarelements, unless stated otherwise. In the drawings, the size of eachelement or a specific portion constituting the element is exaggerated,omitted, or schematically shown for convenience and clarity ofdescription. Thus, the size of each component may not entirely reflectthe actual size. In the case where it is judged that the detaileddescription of the related known functions or constructions mayunnecessarily obscure the gist of the present disclosure, suchexplanation will be omitted.

The present disclosure may include three major components, as shown inFIG. 5 . The first component is a control unit 13, the second one is adetector 14, and the third is an electrode 15. The electrode can be oftwo types. The first possible embodiment of the electrode is the oneshown in FIG. 4 , which involves a magnet 3, a pole piece 4, the firstpole 1 of the electrode and the second pole 8 of the electrode. The roleof the magnet 3 is to increase the depth range at low stimulationcurrents. Together with the pole piece 4, it can linearize andconcentrate parabolic electric field lines in an axial direction aroundthe axis of the first pole 1 of the electrode. This substantiallyresults in a tunnel effect for direction of movement and concentrationof ions as carriers of electrical charges into the intercellular spaces.In this embodiment, the magnet 3 is permanent and has the shape of ahollow cylinder, with the first pole 1 of the electrode, for example ofcopper or brass, passing through its center. In the area of contact withthe skin, the first pole 1 of the electrode is preferably round andcoated with a layer of a suitable material, such as silver. The outercasing and the side of the permanent magnet 3 away from the skin aresurrounded by the pole piece 4 of diamagnetic material. From the sideaway from the skin, the first pole 1 of the electrode is threaded foraffixing a nut 6 and terminates with an adapter 7 for connecting thewire 2. Alternatively, the first pole 1 of the electrode is fixed incombination with a spring and the additional bottom part. The first pole1 of the electrode is unthreaded and has a stop edge matching at least apart of the additional bottom part, wherein the first pole 1 of theelectrode is fixed by a biasing spring member so that the spring membercreates a tension between the first pole 1 of the electrode and,directly or indirectly, the fixing element 5. Thus force is applied inbetween the stop edge of the first pole 1 of the electrode and at leasta part of the additional bottom part, resulting in fixing the first pole1 of the electrode. The annulus-shaped second pole 8 of the electrode issecured to a fixing element 5 while separated from the first pole 1 ofthe electrode by a gap or another insulator. Thus, it is a bipolarelectrode having the fixed position of the first pole 1 of the electrodeand the second pole 8 of the electrode. The magnet 3 is separated fromthe first pole 1 of the electrode by an insulator and possibly also byan air gap. The magnet 3 is oriented with its north pole facing thetissue. The first pole 1 of the electrode, the magnet 3, the pole piece4 and the second pole 8 of the electrode are made of materials intendedfor medical use, and are electrically insulated from each other, exceptfor the area of the magnet 3 pole being in contact with the pole piece.Also, the insulation is of biocompatible material, which is also able towithstand frequent sterilization and is preferably also waterproof.

Preferably, the magnet 3 can be in the form of an electromagnet. Using asuitable source 9, as obvious to those skilled in the art, by means of aadjustable magnetic excitation, it is possible to set the shape of thearea with the highest concentration of the charge carriers, i.e. a kindof a channel. Moreover, if several electromagnets are used, by means oftheir different excitations, it is possible to affect the direction ofelectric current flow to the tissue, i.e. direction of such a channel.As an example, this can be used for finding the desired nerve, even inthe event of inaccurate placement of the electrostimulation device tothe skin.

The DC source 9 is connected between the first pole 1 of the electrodeand the second pole 8 of the electrode. The frequency can be set between1 to 15 Hz and the pulses can be monophasic or biphasic, and forexample, rectangular, sinusoidal or triangular, with exponentialinclines or declines, and widths from 0.1 to 5 ms with a current rangefrom 0 to 50 mA. A frequency from 2 to 6 Hz appears to be the mostpreferred and is very efficient.

Further included is a harness for fixing the device to a particular siteand a power supply. Proper placement of electrostimulation electrodes iscrucial for the efficiency of the entire method and for eliminating therisk of reduced efficiency of the method due to improper handling of theelectrode. The role of the fixing element 5 is to ensure repeatedattachment of the electrodes to the same electrostimulation site. To fixthe position of the electrode, a special harness is used which can usethe shape of a human body as a fixation point to create a shape that ispermanently adapted to the patient and ensures equal conditions for eachstimulation session.

Another embodiment of the electrode is represented by an embodiment witha conductive magnet. This example of a geometrical arrangement of activecomponents is shown in FIG. 1 and FIG. 2 , wherein it includes adiamagnetic wedge 10, the main magnet 11, and the pole piece 4. Thesecomponents provide increased penetration depth of the electric currentflowing between the diamagnetic wedge 10 and the passive conductivecontact 12, even at low stimulation currents. They are, due to theirconfiguration, capable of linearizing and concentrating parabolicelectric field lines in an axial direction around the axis of the mainmagnet 11. This results in an ion channel, limited in the diameter anddirection of ion movement by the magnetic field. Thus, as carriers ofelectric charge into the intercellular spaces, the ions move alongtrajectories determined by magnetic field lines. The diamagnetic wedge10 has two functions. It diverts magnetic field lines from the axis ofthe main magnet 11 and provides electrical connection with the skin. Inthis example, the diamagnetic wedge 10 is made of copper and is in theshape of a cylinder, which is rounded at the end adjacent to the tissuefor better contact with the skin and for maximum possible patientcomfort. As is evident from FIG. 2 , the diamagnetic wedge 10 ispositioned so that it is completely or at least substantially surroundedby the magnetic field of the main magnet 11. In order to perform itsfunction while being easy to maintain, it is further covered with alayer of gold or other non-toxic and inert material conductingelectricity well. The outer casing and the base of the main magnet 11away from the skin are preferably surrounded by the pole piece 4 made ofdiamagnetic material. The diamagnetic wedge 10 on the side away from theskin is connected to the main magnet 11 by means of a conductiveadhesive or other conductive connection, and, in addition to the aboveeffects, it also prevents a so-called magnetic short circuit on the sideof the main magnet 11 oriented towards the skin. In this example, thepassive conductive contact 12 of the electrode is embodied as a thincopper sheet, which can be gold plated but other diamagnetic materialssuch as silver, gold, bismuth, carbon and electrically conductiveplastics of various compositions can be used as well. In the figures,the passive conductive contact 12 of the electrode is annulus-shaped andis attached to the fixing element 5, thereby being separated from themain magnet 11 by a gap filled with the same insulating material ofwhich the fixing element 5 is made. In other embodiments, however, thepassive conductive contact 12 can be represented by various types ofconductive fabrics or any conductive gel or other conductive materialcommonly used in medicine. In this example, the main magnet 11 isrepresented by a neodymium magnet (NdFeB). The main magnet 11 consistsof one or, in alternative embodiments, of several adjacently arrangedmagnets, and it is oriented with its north pole facing the tissue. Thefixing element 5 and the passive conductive contact 12 of the electrodeare made of materials intended for medical use, which are preferablywaterproof and resistant to frequent sterilization. FIG. 3 shows thefield lines of the electrostimulation device.

A source 9 of voltage is connected to the device between the diamagneticwedge 10 and the passive conductive contact 12. Its output values of thesignal shape and frequency are adjustable. Preferably, frequenciesbetween 0.1 to 100 Hz can be used, and the pulse can be monophasic orbiphasic. Pulse shape can be rectangular, sinusoidal or triangular withexponential inclines or declines and the pulse widths from 0.1 to 5 msor precisely from 1 to 3 ms with an amplitude from 0 to 50 mA. Afrequency between 1 to 15 Hz or, more precisely, 2-7 Hz appears to bethe most preferred and very efficient, but each patient may respondoptimally to a different frequency, so individual adjustment plays animportant role.

Another example is a solution of electrostimulation device which doesnot contain a diamagnetic wedge 10, and is thus suitable also for otherapplications, in addition to those described above, such as forstimulating superficial nerves, improving the absorption of substancesthrough the skin, and for a better supply of nutrients to the skin. Fornon-invasive electrical connection with the tissue, this embodiment seesthe base of the main magnet 11 as being in direct contact with the skin.While in the embodiment illustrated in the figures, on the side facingthe skin, i.e. on the side intended to be applied to the skin, the mainmagnet 11 is adapted for non-invasive electrical connection to thetissue by being equipped with a diamagnetic wedge 10. In thisembodiment, the main magnet 11 is, on the side facing the skin, i.e. onthe side intended to be applied to the skin, adapted for non-invasiveelectrical connection to the tissue by being coated at least on a partof the surface with epoxy resin, conductive plastic, or metal such asnickel, silver, carbon, gold or platinum. This is again a bipolarelectrode, in which the main magnet 11 and the passive conductivecontact 12 are firmly fixed in the fixing element 5 relative to oneanother, which is advantageous for re-stimulation of a particular site.As with the other embodiments, it is possible to enhance the effects ofthe magnetic field using pole piece 4 of the main magnet 11 as describedabove, but its use is not required for all applications.

The fixing element can be made of plastic, rubber, or other materialsuch as a neoprene strap or disposable tape, both of which being gluedtogether or otherwise attached.

The device may be used for a treatment of urgent types of incontinenceor an overactive bladder (OAB), for example caused by hypersensitivityin nerve receptors in the bladder. Due to a malfunction in thesereceptors, even when the bladder is one-quarter full, the receptors inthe brain will send a false signal leading to an urgent bladdercontraction. The patient then feels an immediate need to go to thetoilet or, in some cases, urine will leak. The purpose of stimulationusing the proposed device is the transmission of signals throughafferent paths to the brain, which will then restart the receptors inthe bladder and these will then return to a normal state. Further thedevice may be also used for a treatment of neurodegenerative diseasessuch as Parkinson's, Alzheimer's, Huntington's disease, Amyotrophiclateral sclerosis (ALS) or Motor neuron disease.

The electrode 15 system and the detector 14 may be connected via thecontrol unit 13, which controls the entire system. As mentioned above,the system may include a single electrode 15, or more electrodes 15.These can include transcutaneous, percutaneous, or implantableelectrodes. Even when using a single electrode 15, it is possible todetermine the optimal frequency; however, for clinically effectivestimulation of the peripheral nerves, may be necessary to use twoelectrodes. The electrode 15 may be connected to the pulse generator 18.The latter can be of two types. The generator 18 is either directly apart of the electrode 15, i.e. it is located within the electrode 15, orit is external. An external pulse generator 18 can be located in thecontroller 16 or, in case of implantable electrodes 15, it remotelypowers the stimulator.

The detector 14 consists of a sensor 17. In the embodiment of thepresent disclosure, the sensor 17 is an optical sensor 17. The opticalsensor 17 can have several embodiments, but most preferably it is anoptical barrier. An optical sensor 17 assembly is shown in detail inFIG. 6 and is described below in the description of the presentdisclosure. In general, the optical barrier may include a transmitterand a receiver. The transmitter may include a generator 18, an amplifier19 and an infrared diode 20 with the optics. The generator 18 may be setto a frequency of 38 kHz. The receiver may include a diaphragm 21, aconverging lens 22, an infrared filter 23, a preamplifier 24, afrequency filter 25, a demodulator 26, a level converter 27 and aprogrammable retarder 28. The frequency filter 25 may be set to 38 kHz.The following parts can be implemented as one component: converging lens22, infrared filter 23, preamplifier 24, filter 25 and frequencydemodulator 26. In this system of transmitter and receiver, the foot 31may be located between the transmitter output and the receiver input.Other types of optical barriers, such as a reflection optical barrier,are not excluded by the present disclosure. When using a reflectionoptical barrier, the optical sensor 17 can consist of one sensor 17 ormore optical sensors 17 variously spaced on the detector 14. Eachoptical sensor 17 of the reflection optical barrier is a transmitter anda receiver at the same time. This makes it possible to detect an object,which gets into the vicinity of said sensor 17. The first advantage ofan embodiment with multiple optical sensors 17 is that the detector 14does not need to be set up by the operator as precisely for the patientas when using only one sensor 17. Another advantage is that moredetailed information regarding movement is received from several sensors17, which can be further processed by the control unit 13 in detail. Ingeneral, the use of an optical sensor 17 is advantageous in terms ofsimplicity of use because the sensor 17 detects objects with goodaccuracy even when the distance from the sensor 17 can vary each time bya few centimeters. These optical sensors 17 are based on thetransmission of light in the infrared or other spectrum. The sensors 17may also be supplemented with a polarizing filter. In addition to astandard infrared sensor 17, a camera can also be used as an opticalsensor 17. The camera may include a CCD or CMOS camera with sufficientresolution. Further, the optical sensors 17 can be configured tofunction without modulation of the signal, with modulation of the signalfor increased resistance to overloading the optical barrier by ambientlight, or in the infrared region with modulation of signal for increasedresistance to overloading the optical barrier by ambient light.

In one possible configuration, the sensors 17 can be arranged one afteranother. The sensors 17 are placed on the holder, via which they arefirmly attached to the rest of the structure. The holder with thesensors 17 can be adjusted by means of a tightening or locking element.Then the whole system records the movements of the lower limbs, whichare in its vicinity.

In an alternative embodiment, the sensor 17 is used as an accelerometer,which is attached to the patient's body. The use of an accelerometer ismore user-friendly than other sensors. The accelerometer can be attachedto the patient's body using a band to which the accelerometer canpossibly be incorporated into. Further, the accelerometer is capable ofdetecting small changes in position. The accelerometer is attached to apart of the leg and the movements resulting from the stimulation aremeasured by the accelerometer. In an alternative embodiment, capacitive,inductive, thermal, magnetic or ultrasonic sensors 17, direct use of anelectromyograph may be used. The disadvantage, compared to opticalsensors 17, is the smaller distance at which the sensor 17 can detect anobject. An example of an ultrasonic sensor 17 is shown in FIG. 7 . Sucha sensor 17 includes a generator 18 of 50 kHz, an exciter 29, a primarypiezo element 30 and a secondary piezo element 32 at a resonancefrequency of 50 kHz, an amplifier 33, a frequency filter 34 of 50 kHz, ademodulator 26, a level converter 27 and a programmable retarder 28. Inthe case of the sensor 17, the limb 31 is located between the first andthe second piezo elements.

The advantage of the sensor 17 providing a digital signal is also thatthe analog sensors 17 can record the movements induced by the deviceonly via a contact. When recording the induced movements, the contactsensors 17 do not provide a high-quality information, because theynaturally interfere with the observed phenomenon. In some cases itresults in an echo within the sensor 17 caused by multiple recording ofthe same movement. Ultimately, this leads to poor detection quality anderrant determination of improper frequency stimulation, or a differentcharacteristic of voltage for stimulation. Moreover, mechanical sensors17 also need additional components to provide a clear, noise-freesignal.

The contactless sensors 17 or the accelerometer can be used without anymodification between patients. For example, when measuring the inducedspasmodic movement of the feet, the measurement must be individuallycustomized to the patient. The feet and physiology of the movements aredifferent for each patient. When using analog sensors 17, suchcustomization is performed mostly by mechanical/manual re-setting of thesensor 17. This requires technical skill on the part of the operator,usually a doctor. As a result, treatment duration and risk of incorrectrecording by the sensor 17 are increased.

For proper treatment efficiency, the sensor 17 may be capable of sendingthe information related to frequency and preferably also otherinformation related to the patient's body motion, such as range ofmotion or speed. Misuse of the sensors 17, usually contact sensors, aswell as directly switching the stimulation of the patient, constitute asignificant risk and, due to their error rates, do not result in propertherapy. They do not provide any information about frequency or otherparameters, such as range of motion or speed, but they directly affectthe activity of the electrode 15. If the system is operating withinformation on the frequency of movement of a part of the patient'sbody, it can be software-configured to various configurations and canprocess the information differently. This, inter alia, may also provideother advantages, which are described further below. In order to sendthe information on movement frequency, the control unit 13 may beprovided with digital information. Such a device as per the presentdisclosure, can be realized in two ways. Either the direct output fromthe sensor is 17 is digital, or the analog output is connected to theA/D converter, which converts the analog signal to a digital signal andsends it to the control unit 13.

With a digital signal from the sensors 17, the issue of adapting themeasurement for each patient does not arise. All the situations in thiscase are encompassed in the setup of the control unit 13, which takesindividuality into account in advance, and the output from the sensors17 is processed so that it gives the relevant information without anymechanical re-setting of the detector 14. This applies to both thecontactless sensors 17 and the accelerometer, which can be attached tothe foot 31.

The sensor 17 for detecting movement of the stimulated limb sends theinformation to the control unit 13. Here, the information is processedfor further use. The control unit 13 may use the information to directlycontrol the electrodes 15 attached to the patient as feedback foreffective neuromodulation of peripheral nerves. The induced movements ofthe legs may provide clinical information that the set frequency ofstimulation current is correct. Thus, the control unit 13 may be guidedto read the frequency spectrum between the preset limit values. Thesevalues may be already factory-set, and they may be 1 Hz and 100 Hz. Thecontrol unit 13 may control the electrodes 15 in two phases. Thesephases may be the recognition phase and the therapeutic phase. In therecognition phase, the device of the present disclosure searches for anideal frequency or other parameters of the course of current for theindividual patient based on the feedback from the sensor 17. The controlunit 13 system may include the set rules, defining at what point thefrequency of neuromodulation is considered optimum for the patient.Ideally, it is possible to detect each stimulus as a twitch. If thecontrol unit 13 recognizes the ideal frequency, it may be switched to atherapeutic regime. In this mode, the control unit 13 maintains thedetected frequency, thus leading to stimulation of the peripheral nerveswithout further changes. This phase can typically take 30 minutes. Insome cases, for sufficient efficiency of the clinical procedure, thismay take only about two minutes. The control unit 13 can be set toinclude such a condition that once the ideal positive feedback linkagefrom the sensors 17 disappears, the control unit 13 is switched back tothe first recognition phase, and it sets the neighboring frequencies toinitially identified frequencies.

In addition to frequency, the control unit 13 may set other parametersof the pulse as well. One of them is the pulse length, which is between0.1 and 10 ms. Another factor controlled by the control unit 13 is pulseshape. The control unit 13 may also set the voltage polarity rangingfrom positive to negative. Unlike the approach of stimulation by DC, thebiphasic current does not cause electrolysis of tissue, and electrolysispresents a problem for sensitive patients, as it potentially leads toskin problems (irritation of skin, infection). The control unit 13 maybe set in such a way that it calculates the optimum flow of the pulsecurrent x with opposite polarity in order to cancel the effect ofelectrolysis. This mechanism is also known under the term“charge-balanced pulse”. This feature makes the device safer.

In one aspect, the control unit 13 may set the flow of pulse rounds orpulse bursts. This is, for example, 20 pulses applied over a very shorttime. In terms of a longer time interval, these pulse bursts appear as asingle pulse of an irregular shape.

For the above-described pulse setting, a control unit 13 may commandthese parameters is required. As an input for the specific setting, thecontrol unit 13 may use the information from the controller 16 and theinformation on frequency of limb movement from the sensor 17.

Clinical studies have revealed that, for effective treatment, it may benecessary to repeat the therapy in a patient suffering from incontinenceroughly five times before permanent improvement can be achieved. Thisrequires the patient to be subjected to therapy with time breaks whileinevitably passing through both the recognition and the therapeuticphases again; therefore, the control unit 13 includes a memory unitwhere the staff can store data for a single patient, includinginformation relating to at least one identified ideal parameter for agiven patient. The memory of the present disclosure can be any kind ofdata storage, either a local or remote one. These storage devicesinclude HDD and SSD hard drives, flash memories, memory cards, RAMdevices, CDs, DVDs, Blu-ray™ discs, etc. The remote storage unitsinclude the ones that are accessible only by connecting the device to alocal network or the internet, GSM, such as cloud storage. Localnetwork, internet or GSM can all be understood as a network service. Thenetwork may by created also by a number of presented neuromodulationdevices, wherein the first of the neuromodulation devices is connectedto remote storage, and the others are connected to this neuromodulationdevice. The indirect connection of other neuromodulation devicesconnected to the remote storage is preferably wireless. The otherneuromodulation devices communicate with the remote storage unit throughthe first neuromodulation device. The first neuromodulation device thenredirects the data from the remote storage unit to the otherneuromodulation devices connected to the first neuromodulation device asper the identification part of the communicated data.

The stored information about the patient may effectively reduce the timerequired for performing the procedure, and it can also serve asadditional home therapy. In some cases, the patient may buy theelectrodes 15 intended for domestic use for themselves, allowing thepatient or a family member to apply them. This type of device also mayhave a control unit 13 which can use the stored information on theidentified stimulation parameter and adjust the therapy accordingly. Theentry of this information to the device depends on the selected storagemethod, which is not particularly limited by the present disclosure. Ina preferred embodiment, it can be, for example, an SD memory card whichis inserted into the device in the doctors office to identify the idealstimulation parameter and also into the device for home use, where theproper therapeutic settings are as per the identified stimulationparameter. In another preferred embodiment, the selected storage devicecan be e.g. cloud memory. The stimulation parameter can be enteredthrough the device to the cloud storage and made accessible at thedoctor's office or in home therapy by the same or any other device. Thecloud storage and the stimulation parameter entered thereto may also beaccessible through a computer, tablet, mobile phone or other electronicdevice connected to cloud storage.

In addition to reducing the duration of therapy, storing patient datahas other advantages. Thanks to the determination of individualstimulation parameters, there is no need to store this information inanother patient file. On the patient's next visit, it is only necessaryto recall the information automatically from the system with no searchbeing necessary. This also prevents a possible error arising from poorhandwriting. An incorrectly set parameter does not lead to improvementof the patient's condition. The system comprising such information canbe further enhanced by including the statistics that are directlyrelated to the use of the device. In addition to information on aparticular frequency, the system stores other parameters affecting thepulses described above, such as the polarity of pulses, their length,shape, and others. These statistics are also saved to memory where thetherapeutic information is available for a particular patient. Then, theamount invoiced to the patient is always determined correctly andfairly. The same applies to the amount invoiced to the office by thesuppliers in cases when the device in the office is charged according tothe number of treatments performed. It is also possible to work withsuch information as a high-quality source for producing such statistics,which can then be used both for clinical purposes, making it possible topredict the improvement in the patient's condition in the future on thebasis of the recorded treatment. Furthermore, these statistics areuseful for determining the usability of the device, calculating theavoided costs associated with alternative treatments, calculatingservice intervals, and so on.

The control unit 13 of the present disclosure can be unitary, or thedevice can include several control units 13, e.g., one for the detector14 and another for controlling the electrodes 15. If the device involvesseveral control units 13, these units may be equipped with communicationprotocols for continuous information exchange. As a part of thetherapeutic device, the control unit 13 may also serve as adecision-making actor instead of the doctor. In analogue systems, it wasnecessary that the doctor directly set the parameters depending on theobservation of induced movements or depending on the sensor 17 outputfor same. This leads to lower therapeutic efficiency.

The advantage of sending the movement frequency information from thesensor 17 to the control electronics is an increase of the safety andefficiency of the product. With mechanical sensors 17 connected to theelectronics, which use only the amplified signal from the sensor 17 asan excitation signal for stimulation, a potentially dangerous situationcan arise. Due to higher requirements for medical devices, such anapproach may not be feasible in clinical conditions; therefore, a devicemay comprise a control unit 13 with included commands for varioussituations, thus ensuring an increased security. These commands can be apart of the software or firmware of the control unit 13 depending on itstechnical level. The mechanical sensors 17 are also prone to errorconditions. They represent a high risk, specifically in cases in whichthe recording is used as input for stimulation by the electric current.These error conditions can lead to muscle spasm or, worse, to localburns to the patient at the site of the electrode 15. The electronicsable to ensure greater security may require the connection of sensors 17providing digital information. Using a mechanical sensor 17 and safeelectronics would require another link between the sensor 17 and thecontrol unit 13, which would increase the total price of the device aswell as a possible increased failure rate and inaccuracy by addinganother element to the system.

The device may also involve a controller 16. In general, the controller16 may represent an user input for controlling the control unit 13, andthis input can take various shapes and forms. The controller 16 maycomprise the control unit 13 described above. In alternative aspects,the control unit 13 may be located outside the controller 16. Thecontroller 16 may be part of the structure of the entire device but doesnot need to be fixed firmly. The controller 16 can be loosely attachedto the structure, but it can be lockable with respect to the supportstructure in at least one position. In one aspect, the controller 16 mayinvolve a display device and a button. The button connected to thecontroller 16 can be a multistep one, enabling more than one instructionto be given depending on the movement of the controller 16 chosen by theoperator. The display device may be used for transferring theinformation to the operator. After beginning therapy, the display devicecan show the instructions for using the device, so that the therapy isas effective as possible. These can be in the form of a sequence ofinstructions that are shown on the display device one by one by theoperator's clicking on the button of the controller 16. The displayedinformation may be controlled by the control unit 13 of the device.

The method of treatment of incontinence or neurodegenerative diseasessuch as Parkinson's, Alzheimer's, Huntington's disease, Amyotrophiclateral sclerosis (ALS) or Motor neuron disease using theneuromodulation device described above and also other similarneuromodulation devices is further disclosed. Symptoms of an overactivebladder or at least one of the above defined neurodegenerative diseasesare, according to the present disclosure, treated using aneuromodulation device comprising at least two active electrodes capableof generating electrical pulses. The first step of the presentdisclosure is attaching first one active electrode to a patient's legand attaching a second active electrode to any of the patient's legs.Attaching of any of the active electrodes is to be understood asattaching a removable electrode to the patient's skin (transcutaneous)or attaching any of the active electrodes to the patient's body bypenetrating the patient's skin percutaneously or attaching any of theactive electrodes by implanting the active electrodes into the patient'sleg for long-term implantation. Further, the first electrical pulses aregenerated in the first active electrode into the patient's body and thesecond electrical pulses are generated in the second active electrodeinto the patient's body. Further, the present disclosure may involve astep of setting a flow of the current of the pulses. The presentdisclosure may further include a step of synchronizing the timing ofeach pulse.

After generating the electrical pulses, the pulses may be delivered tothe branches of the patient's nerves, thus stimulating the nerves anddelivering the stimulus in the form of the pulse to the target area. Thetarget area may be the sacral plexus or the sciatic nerve. In oneaspect, the first electrical and second electrical pulses are generatedin turns, thus the interval of the electrical pulses can be as follows:the first electrical pulse, then the second electrical pulse, then thefirst electrical pulse, and so on. Alternatively, the interval can be asfollows: the second electrical pulse, the first electrical pulse, thesecond electrical pulse and so on. In some of the preferred embodiments,the electrical pulses can be generated simultaneously at the same timeor can be generated independently, such as the first electrical pulse,the second electrical pulse, the first electrical pulse, and so on. Inone aspect one of the first electrical pulses and one of the secondelectrical pulses reach the target area simultaneously. The simultaneouseffect of two independently generated electrical pulses may bring highereffectivity of the treatment compared to the prior art. According to thepresent disclosure, more than two active electrodes may be used, whereina third active electrode may be attached to the patient's body, forexample, a third active electrode capable of generating electricalpulses may be attached to either of the patient's legs. The thirdelectrode may generate the third electrical pulses, which may besynchronized so that one of the third electrical pulses, one of thesecond electrical pulses and one of the first electrical pulses reachthe target area simultaneously. Similarly, more active electrodes can beattached to the patient's body in order to generate electrical pulses.

The active electrode may be an electrode such as the electrode describedpreviously and illustrated in FIG. 4 , comprising a magnet 3, a polepiece 4, the first pole 1 of the electrode and the second pole 8 of theelectrode. Another embodiment of the electrode is the electrode shown inFIG. 1 . and described previously. Preferably, the electrodes used aretranscutaneous as in the two electrodes described previously or anotherembodiments of transcutaneous electrodes. Transcutaneous electrodes areadvantageous mostly because their usage does not require invasiveprocedures. In yet another embodiment of the disclosure, thepercutaneous electrodes capable of penetrating the patient's skin andcapable of generating electrical pulses are used as active electrodes.In yet another example of the embodiment of the present disclosure, theelectrodes may be long-term implantation electrodes. The electrodes, forexample, the first electrode, the second electrode and the otherelectrodes can involve one or more conductors. The active electrodes ofany type are characterized in that they may be capable of generatingelectrical pulses or capable of delivering the electrical pulsesgenerated by a pulse generator to the body of the patient. The generatormay be either directly a part of the electrode, i.e. it is locatedwithin the electrode, or it is external. An external pulse generator canbe located in the controller or, in case of implantable electrodes, itremotely powers the stimulator. In the embodiment of the presentdisclosure using electrodes for long-term implantation, the electrodescan be inductively “charged”. In this embodiment, the external pulsegenerator is connected to an inductor, and the electrical pulses aregenerated in the electrodes by the magnetic field created by theinductor.

In an aspect of the present disclosure, the active electrodes areattached in proximity to the branches of a peripheral nerve so that theelectrical pulses generated by any of the electrodes are capable ofdelivering electrical pulses to the nerve. When using transcutaneouselectrodes, the electrodes are placed, for example, in the area of theknee so that the surface of the electrodes is facing a branch ofperipheral nerve through the tissue. When using the percutaneouselectrodes or the electrodes for long term implantation, the electrodesmay be placed within the vicinity of the branches of a peripheral nervewhile not directly touching the branches of a peripheral nerve.

In the method of the present disclosure, any of the following nerves arestimulated: the lumbosacral plexus, sciatic nerve, common peroneal,tibial nerve, pudendal nerve, superior gluteal nerve, inferior glutealnerve, posterior cutaneous femoral nerve, obturator internus nerve,piriformis, quadratus femoris nerve, plantar nerve or coccygeal nerve.Most advantageous in treatment of the symptoms of an overactive bladderor a neurodegenerative neurological disease such as Parkinson's,Alzheimer's, Huntington's disease, Amyotrophic lateral sclerosis (ALS),Motor neuron disease is stimulation of the peroneal nerve, pudendalnerve, tibial nerve or any combination of the aforementioned nerves.Stimulation of the nerves is achieved by sending the electrical pulsesthrough the branches of peripheral nerves and distributing the nervestimulus to the target area of, for example, other sacral plexus or thesciatic nerve. The electrodes can be, as per the present disclosure,attached to the patient so that the first active electrode is attachedto the first branch of a sciatic nerve and the second active electrodeis attached to a second branch of the sciatic nerve; in otherembodiments, multiple active electrodes can be attached to multiplebranches of the sciatic or other nerves in order to stimulate the targetarea. The active electrodes can be both attached to the same leg or beeach attached to a different leg of the patient. In some cases,attaching the active electrodes to different legs of the patientincreases the healing effect, as the simultaneous effect of stimulationis more easily achievable.

In the method of treatment, there may be further a grounding conductorplaced on the patient's body. Preferably the grounding conductor is inthe form of a pad. The grounding pad can be placed anywhere on thepatient's body. As per the present disclosure, the grounding conductormay be placed on the patient's suprapubic, hypogastric or sacral area.By placing the grounding conductor in said areas, the healing effect ofthe method increases. For the grounding conductor attracts the first andsecond electrical pulses, thus the target area may be reached moreeffectively. Additionally, the grounding conductor can be configured forgenerating the electrical pulses, wherein in some embodiments, thegrounding conductor generates positive electrical pulses and thus has acalming effect on the patient's bladder.

In the presented method, a variety of electrical pulses may be used. Inone aspect of the present disclosure, the following limitations may beused for the electrical pulses. The frequency of the first electricalpulses, second electrical pulses or, in some embodiments, the pulsesgenerated by a third, a fourth or other electrodes is between 0.1 Hz and100 Hz. Pulse width of said pulses is between 0.1 ms and 5 ms, and thecurrent of said pulses is between 0 mA and 250 mA, with the voltage ofsaid pulses being between 0 V and 90 V. As every patient reacts totreatment differently because of different physiology, the parameters ofpulses therefore vary for individual patients. In one of the preferredembodiments, the parameters vary over the course of the treatment of thepatient according to the patient's response to the treatment. Adjustmentof the parameters can be made by the person providing the treatment orautomatically by means of a control unit having a suitable algorithm.For most patients, the best treatment results may be achieved by usingthe following parameters of said pulses: a voltage frequency of between2.5 Hz and 60 Hz and a pulse width between 0.1 ms and 2.5 ms. TheCurrent of said electrical pulses also depends on the type of theelectrode used and its surface. Using electrodes which have an activesurface of more than 2 cm² achieves the most effective treatment resultsusing a current of the said electrical pulses between 15 mA and 250 mA.Using electrodes which have an active surface of between 0.5 cm² and 2cm² achieves the most effective treatment results using a current ofsaid pulses between 0 mA and 15 mA. Using electrodes which have active asurface of less than 0.5 cm² achieves the most effective treatmentresults using current of said pulses between 0 mA and 5 mA. The shape ofsaid electrical pulses may be also important for improving treatmentresults; most effective is, as per the present disclosure, a shape ofthe electrical pulses having a steep incline. Therefore, an advantageousshapes of said electrical pulses may be substantially rectangular orsubstantially of the shape of right triangle. Said pulses may bemonophasic or biphasic.

In one aspect of the present disclosure, the flow of current may be setcorrespondingly to a biofeedback signal. Such a biofeedback signal canbe visual or determined means of a sensor. Typically, the biofeedbackcan be the form of twitching in the patient's lower limb.

In order to ensure highly effective treatment, said pulses may beapplied to the patient's body in a synchronized manner so that nervestimuli generated in the patient's nervous system by the firstelectrical pulses and the nerve stimuli generated in the patient's bodyby the second electrical pulses reach the target area simultaneously sothat the nerve stimulus generated in the patient's nervous system by anyof the first electrical pulses and the nerve stimulus generated in thepatient's nervous system by any of the second electrical pulses reachthe target area at the same time. In other advantageous aspect of thepresent disclosure, nerve stimuluses may be also generated in thepatient's nervous system by tertiary electrical pulses and/or by anyfurther electrical pulses generated by any other active electrodes,which are synchronized. Synchronization of the pulses may provide moreeffective treatment, so that quicker recovery and shorter treatmentsessions are preferably achieved. Synchronization of the pulses can be,according to one aspect, achieved by means of an algorithm stored in thememory of the control unit, wherein the algorithm sets the timing of thegeneration of the electrical pulses. Multiple inputs can be acquired bythe algorithm, such as data from a sensor monitoring biofeedback,duration, and parameters of the first electrical pulses, secondelectrical pulses and any other electrical pulses, data of the previoustreatment sessions of the patient and other relevant data.

A method of positioning the electrodes is further disclosed, wherein,firstly, an active electrode is attached to the patient's body.Preferably but not exclusively, the attachment is made in the knee areaof the patient. After the attachment, electrical pulses may be generatedin the active electrode. After and/or during the generation of theseelectrical pulses, the reflex movement of the patient's body part ismonitored. The reflex movements of the patient's body part are, forexample, twitches of the lower limb, and such monitoring can be doneeither visually or by sensor. The monitored reflex movement, such as thetwitching of the patient's lower limb, may be thereafter, or during themonitoring, compared to the expected reflex movement. Determination canbe made by the person or by an algorithm. For example, the algorithmcompares the data acquired by the sensor and compares it to the datastored in the memory of the control unit. For example, such data can berepresented by the number of twitches of the limb per period of time. Incase the number of twitches of the lower limb is the same or higher thanthe number of twitches of the lower limb stored in the memory of thecontrol unit, the reflex movement of the patient's body is considered tobe sufficient. Subsequently, the control unit can visually, acousticallyor tactually inform the person of the achievement of sufficient orinsufficient reflex movement of the patient's body part. If the reflexmovement of at least part of the patient's body is insufficient, theelectrode may be relocated on the patient's body and the steps arerepeated. This method enables the user to precisely position the activeelectrode in order to stimulate the nerves of the patient moreeffectively.

The method described above is also suitable for treatment of othermedical conditions, such as and not limited to, painful bladdersyndrome, fecal incontinence, Low Urinary Tract Dysfunction andneurodegenerative diseases such as Parkinson's, Alzheimer's,Huntington's disease, Amyotrophic lateral sclerosis (ALS) or Motorneuron disease.

One of the possible illustrative embodiments of the present method isfurther disclosed. For purpose of this illustrative embodiment, theactive electrode is of a transcutaneous type and the neuromodulationdevice involves two active electrodes, a grounding electrode, a memoryunit, a control unit, a sensor for monitoring the reflex movement of atleast a part of the patient's body, such as an accelerometercommunicatively coupled to the control unit, and a controller forcontrolling the neuromodulation device. A person, such as the patient orthe patient's physician, attaches the active electrode onto thepatient's body. The person may attache the first electrode, for example,in the knee area of the first leg in such manner that the firstelectrode's active surface faces approximately the peripheral nerve. Theperson may further places the grounding electrode, preferably in theform of a pad, on patient's suprapubic, hypogastric or sacral area. Theperson may further place the accelerometer on the patient's leg. Thethen person may activate the device to start generating the firstelectrical pulses. In this illustrative embodiment, the neuromodulationdevice informs the patient of the sufficiency of the induced movementsof the part of the patient's body, in this embodiment, the leg. Theinitial pulses may be generated with parameters according to theprevious treatment sessions of the patient; in cases in which theparameters are not stored in memory, the control unit sets theparameters based on pre-set default parameters. The parameters of thefirst electrical pulses may be any of the following frequency intervals:between 0.1 Hz and 100 Hz, a pulse width of between 0.1 ms and 5 ms, acurrent of between 0 mA and 250 mA, with a voltage between 0 V and 90 V.The control unit may generate the first electrical pulses and changesthe parameters of the pulses. In case, after a predefined number offirst electrical pulses and number of variations of parameter values,the movement of the leg being monitored by the accelerometer isinsufficient, the device may inform the person, for example, audibly orvisually in another manner. For example, by means of a red light, a textdisplay or by means of a predefined sound. The person may thenreposition the first active electrode and repeats the process until themovement of the leg is sufficient. The neuromodulation device may informthe person of sufficient reflex movement either audibly or visually, forexample, by means of, say, a green light or by a text display. Once thefirst active electrode may be precisely attached, the person attachesthe second active electrode to the patient's body. In this illustrativeembodiment, the second active electrode may be attached to the patient'ssecond leg in the knee area in the same way as the first electrode. Thesecond electrode may be further precisely positioned using substantiallythe same steps as in the foregoing precise positioning of the firstactive electrode. As both of the active electrodes may be preciselypositioned to the patient's body, the first electrical pulses and thesecond electrical pulses are directed to the patient's body, stimulatingthe target area. The flow of the pulse current may be set manually or bymeans of the control unit. Preferably, in this illustrative aspect, theparameters of the first electrical pulses and the second electricalpulses are set via the control unit. In this aspect, the synchronizationof the pulses may be achieved by means of the control unit, for example,on the basis of biofeedback, such as the reflex movement of thepatient's leg. The parameters of the pulses might vary during thetreatment session, depending upon the patient's biofeedback. Thetreatment session takes typically 15 to 45 minutes.

In this illustrative aspect information regarding the treatment sessioncan be collected and stored in an adjacent or remote memory storagedevice for further use.

A method of collecting information about usage of a medical device, suchas the neuromodulation device described above, other similarneuromodulation devices or other medical devices are further disclosed.The medical device may comprise a memory and a control unit. Such saidmedical devices can be, for example, therapeutic medical devices,surgical devices or diagnostic medical devices. The method may involvethe first step, where information from the control unit is collected,after that the collected information is sent from the control unit tomemory. After sending the information to the memory. the information maybe stored in a database. The information stored in the database may belater called out from the database, for example, by using a controlpanel, computer or other electronic device with access to the database.The control unit can communicate with the memory using a variety ofcommunication protocols, such as but not limited to GSM, Bluetooth,radio frequency, infrared communication, LAN, USB and a wirelessinternet connection. In one aspect, the memory can be remote from themedical device, such being stored on the cloud, remote server or remotedata storage. In one aspect, an identification number may be assigned tothe medical device and/or to a patient. In one aspect, theidentification number is assigned also to the particular information.According to the identification number, the memory can assign paymentand suitable treatment parameters for the patient. For example, using amedical device and a memory of a remote type, any medical device cancall information about the patient and adjust treatment parametersaccording to the patient's needs; payment can also be directedaccordingly to the patient's identification number. Accessing the remotememory of the medical device can be achieved by connecting to remotememory, such as the cloud, or by connecting to the memory adjacent tothe medical device through a connection established in between themedical devices. In one aspect, several medical devices can create acommunication network, with one of the medical devices being able toconnect to the memory and other medical devices being able to access thememory by communicating with the said one medical device.

In one aspect, the information stored in the database may be sent to thepatient's physician and/or to the patient's electronic medical chart.Sending the information automatically or upon the patient's requestthrough the device is convenient for the patient and patient'sphysician, especially during home treatment applied by the patienthimself. The data stored in the database can also be used for evaluatingthe progress of each user. Also, the information stored in the databasecan provide a long-term statistical record of the usage of the medicaldevices. Such feedback may be important for the manufacturer tofine-tune the device accordingly and to have sufficient data fordevelopment of the devices. Information used for such long-termstatistics, for example, data on usage of neuromodulation devices, maybe any the following: the data on the number of users, data on theintensity of usage, on the number of payments, on current intensity oron frequency of pulses.

The inventors surprisingly found the above defined methods may beapplicable also for a neuromodulation treatment of neurodegenerativediseases as follows.

The above-mentioned methods may include a method for a neuromodulationtreatment of a patient and may be used for the treatment of aneurodegenerative disease. In such case the method for a neuromodulationtreatment of a neurodegenerative disease may comprise: attaching a firstactive electrode to a first patient's leg in the back of the knee areain an expected location of a peroneal nerve of the first leg; attachinga grounding electrode to the patient's body; generating electricalpulses by a pulse generator connected to the first active electrode andthe grounding electrode; stimulating by the first active electrode theperoneal nerve of the first leg; and controlling via a control unit aflow of the generated pulses to the first active electrode.

The method for a treatment of a neurodegenerative disease may furthercomprise: attaching a second active electrode to a second patient's legin the back of the knee area in an expected location of a peroneal nerveof the second leg; generating electrical pulses by the pulse generatorconnected to the second active electrode; stimulating by the secondactive electrode the peroneal nerve of the second leg; and controllingvia a control unit a flow of the generated pulses to each of the firstand second active electrode.

Alternatively, the method for a neuromodulation treatment of aneurodegenerative disease may comprise: attaching a first activeelectrode to a first patient's leg in the back of the knee area in anexpected location of a tibial nerve of the first leg; attaching agrounding electrode to the patient's body; generating electrical pulsesby a pulse generator connected to the first active electrode and agrounding electrode; stimulating by the first active electrode thetibial nerve of the first leg; and controlling via a control unit a flowof the generated pulses to the first active electrode.

Such alternative method for a treatment of a neurodegenerative diseasemay further comprise: attaching a second active electrode to a secondpatient's leg in the back of the knee area in an expected location of atibial nerve of the second leg; generating electrical pulses by thepulse generator connected to the second active electrode; stimulating bythe second active electrode the tibial nerve of the second leg; andcontrolling via a control unit a flow of the generated pulses to each ofthe first and second active electrode.

In the method for a treatment of a neurodegenerative disease, theneurodegenerative disease may include Parkinson's, Alzheimer's,Huntington's, Amyotrophic lateral sclerosis (ALS) or Motor neurondisease.

Stimulating of the first and the second peroneal nerve may involve asimultaneous stimulation of the first and the second peroneal nerve.Alternatively stimulating of the first and the second tibial nerve mayinvolve a simultaneous stimulation of the first and the second tibialnerve.

Controlling may involve setting voltage and/or current of the generatedpulses to invoke a reflex movement of each of the first and the secondpatient's leg. The grounding electrode may be attached to patientssuprapubic or sacral area. The generated electrical pulses may beelectrical pulses with a frequency comprised between 2.5 Hz and 60 Hzand the electrical pulses may have a pulse width comprised between 0.1ms and 2.5 ms. The frequency of the electrical pulses may be comprisedbetween 0.5 Hz and 10 Hz. Thus, the frequency of the electrical pulsesmay be 0.5 Hz, 1 Hz, 2 Hz, 3 Hz, 4 Hz, 5 Hz, 6 Hz, 7 Hz, 8 Hz, 9 Hz or10 Hz. The frequency of the electrical pulses may be comprised between2.5 Hz and 10 Hz. The frequency of the electrical pulses may becomprised between 2.5 Hz and 6 Hz. The voltage of the generatedelectrical pulses may be less than 90 V and current of the electricalpulses may be lower than 250 mA. Each of the active electrodes may havean active conductive surface attached to a patient's leg comprisedbetween 0.0775 square inch (0.5 cm²) and 0.3100 square inch (2 cm²).Each of the active electrodes may have an active conductive surfaceattached to a patient's leg less than 0.0775 square inch (0.5 cm²). Eachof the active electrodes may have an active conductive surface attachedto a patient's comprised between 0.0155 square inch (0.1 cm²) and 0.0775square inch (0.5 cm²).

The method for a neuromodulation treatment of a low urinary tractdysfunction may further comprise detecting a reflex movement of each ofthe first and the second patient's leg. The reflexive movement may be aresponse to the first and/or the second peroneal nerve stimulation. Thereflexive movement may be a periodical reflexive movement in atransversal plane of a foot belonging to the respective first and secondpatient's leg. Alternatively, the reflexive movement may be a responseto the first and/or the second tibial nerve stimulation. The reflexivemovement may be a periodical reflexive movement in a transversal planeof a foot belonging to the respective first and second patient's leg.

The method for a treatment of a neurodegenerative disease may furthercomprise monitoring the reflexive movement of each of the first and thesecond patient's leg; comparing the monitored reflex movement with apre-set value of an expected reflex movement and based on the comparisondetermining whether the reflex movement is sufficient.

The method for a treatment of a neurodegenerative disease may furthercomprise determining frequency of the periodical reflexive movement foreach of the first and the second patient's leg. Controlling may theninvolve an automatic setting of the flow of the generated pulses to eachof the first and the second active electrode depending on the determinedfrequency of the periodical reflexive movement of each of the first andthe second patient's leg. The automatic setting of the flow may theninvolve setting timing of generated pulses to each of the first and thesecond active electrode so that the periodical movements of thereflexive movement of the first and the second leg are synchronized.

The method for a treatment of a neurodegenerative disease may furthercomprise collecting information from the control unit about the flow ofthe pulses and storing the information in a database. The informationmay comprise current of the pulses, frequency of the pulses and aninformation of the treatment duration.

The expected location of a target nerve may be a generically knownlocation onto a patient skin closest to the target nerve or inside ofthe patient body closest to the target nerve. Generic locations ofnerves within a human body are known, however, as they differ perperson, the expected location of the target nerve might not be theactual closest location to the person's target nerve.

Attaching an electrode to a patient may mean attaching the electrodeonto the skin of the patient and/or attaching the electrode into thepatient's body.

Exemplary Study Showing an Effect of the Method on Brain

An exemplary study was designed and performed to test that theabove-described method and its variances induces desired changes in theneuronal activity in the brain. A total of 22 healthy volunteers wereenrolled into the study. All volunteers underwent an active peronealnerve stimulation using the above-described method, which in allvolunteers elicited a motor response in the form of rhythmic movement ofboth feet in the transverse plane. Subsequently, an identical feetmovement was induced in all volunteers passively using a speciallydesigned “sham” device without a simultaneous neuromodulation. This madepossible to distinguish changes in neuronal activity during passive feetmovements by the “sham” device from changes elicited by theneurostimulation using the above-described method. Simultaneousfunctional magnetic resonance imaging (fMRI) was employed to measurechanges in neuronal activity. The fMRI enables a detection of a localchange/increase in blood supply in the brain tissue, which correlateswith an increase of a neuronal activity.

The neuromodulation was performed within a non-limiting frequency rangeof the electrical pulses between 0.1 to 10 Hz, however, similarresponses were observed in both higher and lower frequencies. Therefore,the neuromodulation may be performed at 0.5 Hz, 1 Hz, 2 Hz, 3 Hz, 4 Hz,5 Hz, 6 Hz, 7 Hz, 8 Hz, 9 Hz or 10 Hz.

Two active electrodes were attached one per each leg of the studysubjects. Each electrode was attached in the back of the knee of therespective leg. One electrode on one leg may however suffice.

All fMRI data were acquired with a 3T MRI scanner and analyzed usingindividual and group statistical analysis (p<0.05). Statistical analysison the individual level assessed twelve selected brain regions and themask for each specific region was used to acquire statisticallysignificant voxels of activation within these regions. The resultingindividual statistical maps were subsequently included in groupstatistics using a one-sample t-test and an uncorrected threshold ofp=0.001.

Results of the study provide evidence that the above-describedneuromodulation method elicits a statistically significant activation ofspecific brain regions such as basal ganglia, limbic system and otherthat are linked with an early stage of neurodegenerative diseases suchas Alzheimer's dementia or Parkinson's disease. The results aresummarized in the Table 1 below. The inventors believe that activationof the specific brain regions, associated with an increase in bloodflow, helps to improve its metabolism and function. This could lead tothe preservation of the neural function (neurorehabilitation) andprevent or delay the onset of clinical symptoms of neurodegenerativediseases.

TABLE 1 Peroneal Placebo Brain Stem 0.435 0.667 Cerebellum R 0.014 L0.004 Thalamus R 0.599 L 0.212 Putamen R 0.033 L 0.026 Cingulate gyrusmiddle R 0.287 L 0.373 Insula anterior R 0.022 L 0.049 0.556 posterior R0.305 0.556 L 0.204 0.394 Operculum parietal R 0.011 0.002 L 0.007 0.001central R 0.048 L 0.040 0.475 Precentral gyrus R 0.021 0.005 L 0.0120.002 Postcentral gyrus R 0.029 0.023 L 0.027 0.015 Supplementary motorcortex R 0.031 L 0.033 Temporal gyrus superior R 0.460 L 0.309transverse R 0.392 L 0.120 0.186 Angular gyrus R 0.676 L Supramarginalgyrus R 0.001 0.124 L 0.001 Frontal gyrus superior R 0.204 0.067 L 0.169middle R 0.236 L inferior R 0.007 L 0.046

The results of the study are also graphically presented in FIGS. 8 to 10depicting statistically averaged details of the fMRIs performed.

More specifically, FIG. 8 depicts statistically adjusted results offMRIs performed on subjects with a “sham” where a motoric responseobserved during the peroneal neuromodulation were imitated without theactual neuromodulation. An increase of a blood flow/neuronal activity isvisible mostly in superficially located centers including precentralgyrus, postcentral gyrus and operculum as a response to the passive feetmovement.

FIGS. 9 . and 10. then depict statistically adjusted results of fMRIsperformed on subjects during the neuromodulation.

More specifically FIG. 9 . shows an expected increase of the bloodflow/neuronal activity in the cortical centers involved in the controlof the lower limbs (both motor and sensory). In contrary to the “shamstimulation”, there is an evident significant increase of the bloodflow/neuronal activity in deep brain centers associated with the lowerurinary tract function including cerebellum, putamen, insula,supplementary motor cortex and frontal cortex. FIG. 10 . shows theresults after applying the specific software mask, that allows fordetailed analysis of the basal ganglia. There is a significant increaseof blood flow/neuronal activity detected during peronealneuromodulation.

Therefore, Table 1. as well as both FIG. 9 . and FIG. 10 . confirm thatperoneal neuromodulation leads to a significant increase of bloodflow/neuronal activity in the deep brain structures including midbrainand basal ganglia playing crucial role in the pathogenesis of theseveral neurodegenerative diseases such as Alzheimer's dementia orParkinson's disease.

LIST OF REFERENCE SIGNS

-   1—first pole of the electrode-   2—wire-   3—magnet-   4—pole piece-   5—fixing element-   6—nut-   7—adapter-   8—second pole of the electrode-   9—source-   10—diamagnetic wedge-   11—main magnet-   12—passive conductive contact-   13—control unit-   14—detector-   15—electrode-   16—controller-   17—sensor-   18—generator-   19—amplifier-   20—IR diode-   21—diaphragm-   22—converging lens-   23—IR filter-   24—preamplifier-   25—frequency filter-   26—demodulator-   27—level converter-   28—programmable retarder-   29—exciter-   30—first piezo element-   31—foot-   32—second piezo element-   33—amplifier-   34—frequency filter

The invention claimed is:
 1. A method for a neuromodulation treatment ofa patient having an either one of Parkinson's, Alzheimer's, Huntington'sdisease, Amyotrophic lateral sclerosis and Motor neuron disease, themethod comprising: attaching a first active electrode to a first leg ofthe patient in the back of the knee area in an expected location of aperoneal nerve of the first leg; attaching a grounding electrode on thepatient's body; generating electrical pulses by a pulse generatorconnected to the first active electrode and a grounding electrode;stimulating by the first active electrode the peroneal nerve of thefirst leg and activating via the stimulation brain regions linked withthe disease, wherein the activation of the brain regions comprises anincrease of blood flow/neuronal activity in the brain regions of at lastone of limbic system, basal ganglia and/or a midbrain of the patient;and controlling via a control unit a flow of the generated pulses to thefirst electrode.
 2. The method of claim 1, further comprising: attachinga second active electrode to a second leg of the patient in the back ofthe knee area in an expected location of a peroneal nerve of the secondleg; generating electrical pulses by the pulse generator connected tothe second active electrode; stimulating by the second active electrodethe peroneal nerve of the second leg and activating via the stimulationbrain regions linked with the disease, wherein the activation of thebrain regions comprises an increase of blood flow/neuronal activity inthe brain regions of at least one of a limbic system, basal gangliaand/or a midbrain of the patient; and controlling via a control unit aflow of the generated pulses to each of the first and second activeelectrode.
 3. The method of claim 2, wherein stimulating of the firstand the second peroneal nerve involves a simultaneous stimulation of thefirst and the second peroneal nerve.
 4. The method of claim 2, whereincontrolling involves setting voltage and; or current of the generatedpulses to invoke a reflex movement of each of the first and the secondleg of the patient.
 5. The method of claim 4, wherein the reflexivemovement is a periodical reflexive movement in a transversal plane of afoot belonging to the respective first and second leg of the patient. 6.The method of claim 2, further comprising: detecting a reflex movementof each of the first and the second lot of the patient, wherein thereflexive movement is a response to the first and/or the second peronealnerve stimulation.
 7. The method of claim 6, the method furthercomprising: monitoring the reflexive movement of each of the first andthe second leg of the patient; comparing the monitored reflex movementwith a preset value of an expected reflex movement and based on thecomparison determining whether the reflex movement is sufficient.
 8. Themethod of claim 7, the method further comprising: determining frequencyof the periodical reflexive movement for each of the first and thesecond leg of the patient.
 9. The method of claim 8, wherein controllinginvolves an automatic setting of the flow of the generated pulses toeach of the first and the second active electrode depending on thedetermined frequency of the periodical reflexive movement of each of thefirst and the second leg of the patient.
 10. The method of claim 8,wherein the automatic setting of the flow involves setting timing ofgenerated pulses to each of the first and the second active electrode sothat the periodical movements of the reflexive movement of the first andthe second leg are synchronized.
 11. The method of claim 2, wherein eachof the active electrodes has an active conductive surface attached tothe first or the second leg of the patient comprised between 0.0775square inch (0.5 cm2) and 0.3100 square inch (2 cm2).
 12. The method ofclaim 2, wherein each of the active electrodes has an active conductivesurface attached to the first or the second leg of the patient less than0.0775 square inch (0.5 cm2).
 13. The method of claim 2, wherein each ofthe active electrodes has an active conductive surface attached to thefirst or the second leg of the patient comprised between 0.0155 squareinch (0.1 cm2) and 0.0775 square inch (0.5 cm2).
 14. The method of claim1, wherein the grounding electrode is attached to patient's suprapubicor sacral area.
 15. The method of claim 1, wherein the generatedelectrical pulses are electrical pulses with a frequency comprisedbetween 2.5 Hz and 60 Hz and the electrical pulses have a pulse widthcomprised between 0.1 ms and 2.5 ms.
 16. The method of claim 1, whereinthe frequency of the electrical pulses is comprised between 0.5 Hz and10 Hz or between 2.5 Hz and 10 Hz.
 17. The method of claim 1, whereinthe frequency of the electrical pulses is comprised between 2.5 Hz and 6Hz.
 18. The method of claim 1, wherein the voltage of the generatedelectrical pulses is less than 90 V and current of the electrical pulsesis lower than 250 mA.